A cohort of patients with chronic type B hepatitis has been followed regularly with frequent determinations of routine serum biochemical liver tests as well as serological markers of hepatitis B virus infection. Selected individuals have been entered into therapeutic trials of antiviral and immunomodulating therapies. Three forms of therapy have been investigated: 1) adenine arabinoside monophosphate (Ara-AMP), 2) corticosteroids and 3) recombinant DNA human leukocyte alpha interferon (IFN). A total of 26 patients were treated with Ara-AMP in various dosage regimens over the past 3 years. Long-term follow-up has demonstrated that only 2 of the 26 (8%) have had a sustained beneficial clinical remission in response to therapy. This rate of response is similar to the spontaneous rate of remission in untreated controls. A short course of high dose prednisolone therapy was given to 10 patients in a randomized, double blind controlled trial. During a one-year follow-up, none of the 10 predniosolone-treated and none of five placebo-treated patients underwent a remission in the disease. Indeed, in three treated patients the disease activity increased. In a pilot study, eight patients were treated with multiple courses of a highly purified recombinant human leukocyte interferon. Subsequently, a sustained clinical and serological remission occurred in two of the eight patients. A randomized controlled trial of a four-month course of recombinant human leukocyte interferon has been begun.